Potassium Phosphate, Tribasic → 8-(4-Bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

HRID 2067026노트

반응식

HRID 2067026 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1Cl)=[O:4].[Br:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([Cl:23])[CH:17]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:20][C:19]1[CH:21]=[CH:22][C:16]([Br:15])=[CH:17][C:18]=1[Cl:23])=[O:4]

참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 6101694-Bromo-2-chloroanilineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 59565199Methyl 8-chloroimidazo[1,5-a]pyridine-7-carboxylate

생성물 1

HCID 595652138-(4-Bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester수율 50%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
110 °C

실험 절차

A suspension of 8-chloro-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (300 mg, 1.43 mmol), 4-bromo-2-chloroaniline (354 mg, 1.72 mmol), Pd2dba3 (65 mg, 0.07 mmol), 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (131 mg, 0.28 mmol) and K3PO4 (424 mg, 2.00 mmol) in toluene (5 ml) was degassed and then heated at 110° C. for 18 hours. The reaction mixture was then cooled to room temperature and diluted with ethyl acetate. The resultant mixture was washed with water and brine, then loaded onto a 10 g Isolute® SCX-2 cartridge which was eluted with methanol and then a 2M solution of ammonia in methanol. The appropriate fractions were combined and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 100%, ethyl actetate in DCM) to afford the title compound as a yellow oil (271 mg, 50%). LCMS (method B): RT=3.65 min, [M+H]+=381/383.

후처리

  1. customwas degassed
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washThe resultant mixture was washed with water and brine
  5. washwas eluted with methanol
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-1af585ebf4b54b31aeb5f21a83039607
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293763B2

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